American Journal of Nephrology最新文献

{"title":"Kidney Amyloidosis: Updates on Pathogenesis and Therapeutic Frontiers.","authors":"C Elena Cervantes, Mohamed G Atta","doi":"10.1159/000539596","DOIUrl":"10.1159/000539596","url":null,"abstract":"<p><strong>Background: </strong>Amyloidosis includes a diverse group of rare diseases characterized by the misfolding of native or mutant proteins, leading to extracellular accumulation in various organs. While 42 proteins have been identified to date, their distribution differs between systemic and localized forms.</p><p><strong>Summary: </strong>Mass spectrometry analysis of tissue samples in the USA shows immunoglobulin light chain (AL) amyloidosis as the most prevalent systemic type, followed by transthyretin (ATTR). Heart and kidney involvements are common. Although there are 14 recognized types of kidney-related amyloidosis, clinicopathologic studies in the USA have identified 11 types, with AL amyloidosis being the most prevalent cause of kidney involvement.</p><p><strong>Key messages: </strong>This review focuses on AL, AA, and ATTR amyloidosis due to their common systemic presentations. Recent US-based clinicopathologic studies challenge conventional beliefs that toxicity is primarily driven by amyloid deposition and highlight the role of the complement pathway. Diagnostic methods, particularly mass spectrometry, are crucial for accurate typing. Treatment strategies vary depending on the underlying type, with AL amyloidosis primarily targeting plasma cell clones, AA amyloidosis addressing underlying inflammation with systemic therapies, and ATTR amyloidosis focusing on ATTR stabilization or gene silencing.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"249-260"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upacicalcet Preserves Albumin Levels in Patients on Hemodialysis with Secondary Hyperparathyroidism: A post hoc Analysis of a Randomized Trial.","authors":"Hirotaka Komaba, Seigo Akari, Yoshiyuki Ono, Masafumi Fukagawa","doi":"10.1159/000548738","DOIUrl":"10.1159/000548738","url":null,"abstract":"<p><strong>Introduction: </strong>Parathyroid hormone (PTH) induces browning of adipose tissue, leading to increased resting energy expenditure and loss of adipose and muscle tissues in animal models of kidney failure. However, its clinical significance in humans remains unclear. This study aimed to investigate whether PTH-lowering therapy with upacicalcet, a novel injectable calcimimetic, affects serum albumin levels as a surrogate marker of protein-energy wasting in patients on hemodialysis with secondary hyperparathyroidism (SHPT).</p><p><strong>Methods: </strong>This was a post hoc analysis of a phase 3, double-blind, placebo-controlled study of upacicalcet for the treatment of SHPT in patients on hemodialysis. Participants were randomized in a 2:1 ratio to receive either upacicalcet or placebo after each hemodialysis session for 24 weeks. Longitudinal changes in serum albumin levels were compared between groups using mixed-effects models for repeated measures. The rate of change (slope) in serum albumin over time was also estimated using a linear mixed-effects model.</p><p><strong>Results: </strong>A total of 99 patients in the upacicalcet group and 46 patients in the placebo group were included in the analysis. While serum albumin levels tended to decline in the placebo group, they remained relatively stable in the upacicalcet group, with a significant treatment-by-time interaction. In the linear mixed-effects model, the slope was less steep in the upacicalcet group than in the placebo group, although the between-group difference (0.09 g/dL per year; 95% CI, -0.04 to 0.23) did not reach statistical significance.</p><p><strong>Conclusion: </strong>These findings raise the hypothesis that PTH suppression with upacicalcet mitigates the gradual decline in serum albumin levels over time. Further studies are warranted to investigate the long-term impact of PTH control on protein-energy wasting and related clinical outcomes.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"461-467"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13384445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Earlier Hematuria Negative Conversion Was an Independent Predictor for Nephrotic Remission in Patients with Primary Membranous Nephropathy and Nephrotic Syndrome.","authors":"Qing-Lian Hu, Gang Wang, Wen-Na Song, Xu Liu, Qi-Dong Zhang, Hong-Dong Huang, Ai-Hua Zhang","doi":"10.1159/000549081","DOIUrl":"10.1159/000549081","url":null,"abstract":"<p><p><p>Introduction: Prognostic value of glomerular hematuria in primary membranous nephropathy (PMN) patients with nephrotic syndrome (NS) has not been well understood. We investigated the earlier improvement of hematuria in PMN patients with NS receiving immunosuppressive (IS) therapies to illuminate its prediction capacity for the treatment response and remission status at 12 months.</p><p><strong>Methods: </strong>This is a single-center retrospective study. From 1 January 2021 to 30 June 2024, patients with biopsy-proven PMN and NS starting IS therapy after renal biopsy were recruited. The main exposures were baseline hematuria and hematuria disappearing at 6 months. The outcome was nephrotic remission status at 12 months. Binary logistic regression models were used to estimate the relationship between exposures and outcomes. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive performance of exposures.</p><p><strong>Results: </strong>Overall, 127 patients met the eligibility criteria. Overall, 112 patients (88.2%) had glomerular hematuria at the renal biopsy. Patients with hematuria had higher ages (57.2 ± 12.4 vs. 47.9 ± 12.7, p = 0.007), higher serum h-CRP levels (1.14 [0.66, 2.11] vs. 0.41 [0, 0.91], p = 0.004), and lower remission rate at 12 months (66/112 [58.9%] vs. 13/15 [86.67%], p = 0.037). In the subgroup of patients with glomerular hematuria, baseline hematuria levels were 18 (8, 25) RBC/μL. No significant correlations were found between baseline hematuria levels and other clinical indexes. At 6 months, 31 out of 112 (27.7%) patients had negative conversion of hematuria, and they had lower baseline PLA2R Ab titer (43.6 [0, 78.2] vs. 67.5 [10.8, 191.4], p = 0.025) and higher nephrotic remission rates at 12 months (26/31 [83.9%] vs. 40/81 [49.4%], p = 0.037), compared with those without. There were no significant differences among IS agents between the groups. Binary logistic regression demonstrated that hematuria disappearance at 6 months was an independent predictor for nephrotic remission at 12 months (OR = 0.211, 95% CI: 0.070-0.635, p = 0.006). ROC curve analysis revealed that the area under the curve for forecasting nephrotic remission at 12 months was 0.643 (p = 0.010) independently by the hematuria disappearance at 6 months and 0.781 (p < 0.001) combined with PLA2R Ab titer and IS therapeutic programs.</p><p><strong>Conclusions: </strong>Patients with PMN and NS have high prevalence of glomerular hematuria. Patients without hematuria or negative conversion of hematuria at 6 months after IS treatment have higher nephrotic remission rates at 12 months. For patients with hematuria, hematuria disappearance at 6 months was an independent predictor for nephrotic remission at 12 months. </p>.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"395-404"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12707887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Proteins for Prediction of Kidney Disease Progression and Cardiovascular Outcomes: Individual Participant Data Meta-Analysis of Four Cohorts.","authors":"Carolina Lopez-Silva, Aditya Surapaneni, Josef Coresh, Teresa K Chen, Pascal Schlosser, Eugene P Rhee, Sushrut S Waikar, Insa M Schmidt, Rajat Deo, Peter Ganz, Ruth Dubin, Vasan S Ramachandran, Paul L Kimmel, Sarah J Schrauben, Chirag R Parikh, Joseph V Bonventre, Mirela Dobre, Panduranga S Rao, Ana C Ricardo, Matthew R Weir, Morgan E Grams","doi":"10.1159/000547138","DOIUrl":"10.1159/000547138","url":null,"abstract":"<p><strong>Introduction: </strong>KIM-1, TNFRSF1A, and TNFRSF1B have been accepted as early risk markers in diabetic kidney disease by the US Food and Drug Administration. Whether they may be useful in identifying high-risk patients for cardiovascular/kidney clinical trial enrollment in other important subgroups is uncertain.</p><p><strong>Methods: </strong>We evaluated the potential prognostic enrichment of KIM-1, TNFRSF1A, and TNFRSF1B in four cohorts: the Atherosclerosis Risk in Communities (ARIC) (N = 4,594, mean age 76 years, 55% women, mean eGFR 68 mL/min/1.73 m2), African American Study of Kidney Disease and Hypertension (AASK) (N = 705, mean age 55 years, 39% women, mean mGFR 46 mL/min/1.73 m2), Chronic Renal Insufficiency Cohort (CRIC) (N = 2,943, mean age 59 years, 45% women, mean eGFR 35 mL/min/1.73 m2), and Boston Kidney Biopsy Cohort (BKBC) (N = 434, mean age 54 years, 48% women, mean eGFR 51 mL/min/1.73 m2). We evaluated three outcomes: 40% glomerular filtration rate (GFR) decline, kidney failure, and incident cardiovascular disease (CVD) overall and in two subgroups historically underrepresented in clinical trials: participants with no diabetes, and those with albuminuria <200 mg/g.</p><p><strong>Results: </strong>Published models (40% decline tool, kidney failure risk equation, and PREVENT) using clinical variables had moderate to strong risk discrimination in each cohort: 40% GFR decline, AUROC range: 0.78-0.90; kidney failure, C-statistic range: 0.75-0.93; and CVD, C-statistic range: 0.59-0.79. After addition of biomarkers, there was a small but significant improvement in the meta-analyzed overall population: change in AUROC in 40% GFR decline: 0.02, p < 0.001; change in C-statistic for kidney failure: 0.01, p = 0.02; change in C-statistic for CVD: 0.01, p = 0.03. Among participants without diabetes, the change was statistically significant only for 40% decline; among patient with albuminuria <200 mg/g, the change was statistically significant only for the two kidney outcomes.</p><p><strong>Conclusion: </strong>KIM-1, TNFRSF1A, and TNFRSF1B may not be strong prognostic enrichment biomarkers over and above clinical risk estimates. Clinical trials should test whether they help with predictive enrichment.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"328-339"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Statement.","authors":"","doi":"10.1159/000553196","DOIUrl":"10.1159/000553196","url":null,"abstract":"<p><p>The article \"Tonsillar CD4+CD25+ Regulatory T Cells from IgA Nephropathy Patients Have Decreased Immunosuppressive Activity in Experimental IgA Nephropathy Rats\" [Am J Nephrol. 2013;37(5):472-480; https://doi.org/10.1159/000350533] by Hongdong Huang, Youming Peng, Xi-Dai Long, Zhihua Liu, Xiaojun Wen, Meng Jia, Yumei Liang, and Anlan Huang has been retracted by the Publisher and the Editor.After the publication of this article, image duplication was identified between Figure 3 (TGF-β1) and Figure 3 (β-actin) of this article and Figure 3 (ADAMTSI3-antibody) and Figure 3 (β-actin), respectively, in a later published article by overlapping authors [1]. Image duplication was also detected between the panels within Figure 4 of this article.When asked to comment, the corresponding author stated that the original data for Figure 3 was not available for review and did not provide an explanation for the overlapping images. The authors provided an original image for Figure 4. The concerns and authors' response were reviewed by the Editor, who determined that the response was unsatisfactory to resolve the concerns and concluded that, as the concerns are not resolved and may impact the reliability of the article, the article should be retracted.Hongdong Huang disagrees with the retraction, and the co-authors did not respond to our correspondence about the retraction of this article within the timeframe specified or could not be reached for comment.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"667-668"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Power of Multiple Artificial Intelligence Models to Predict Global Chronic Kidney Disease Incidence: Who Leads the Race?","authors":"Jianbo Qing, Wisit Cheungpasitporn, Kaili Qin, Xiao Wang, Yafeng Li, Junnan Wu","doi":"10.1159/000549005","DOIUrl":"10.1159/000549005","url":null,"abstract":"<p><strong>Introduction: </strong>The global incidence of chronic kidney disease (CKD) continues to rise, but delayed epidemiological data pose challenges to public health policy. Traditional surveillance methods often suffer from reporting delays. Recent advances in artificial intelligence (AI) offer novel opportunities for enhancing disease burden predictions.</p><p><strong>Methods: </strong>We collected CKD incidence data from 21 Global Burden of Disease (GBD) regions spanning from 1990 to 2021. Using five advanced AI models (GPT-4o, Claude-3.7, DeepSeek-R1, Grok-3, and Gemini 2.5) and two traditional forecasting methods (autoregressive integrated moving average and Bayesian age-period-cohort), we predicted CKD incidence for 2023. The performance of the models was evaluated by comparing the predicted values to the actual observed data. All models were trained using the same data and instructions.</p><p><strong>Results: </strong>The AI models and traditional models performed similarly, with near-perfect accuracy in predicting incidence rates in regions such as the Americas, Central Europe, East Asia, high-income Asia Pacific, Southeast Asia, and tropical Latin America. Among the models, GPT-4o demonstrated the highest mean accuracy of 0.722, with all models achieving average accuracies above 0.65. No statistically significant difference in accuracy was observed between AI-based and traditional models (ANOVA p = 0.27).</p><p><strong>Conclusion: </strong>State-of-the-art AI models, when systematically prompted and standardized, can predict global CKD incidence with accuracy comparable to traditional statistical models. AI-driven epidemiological forecasting holds promise for enhancing real-time public health planning and resource allocation, particularly in regions with stable historical data.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"654-663"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy and Cellular Therapies for Cancers in Kidney Transplant Patients.","authors":"Massini Merzkani, Rose Mary Attieh, Kenar D Jhaveri, Naoka Murakami","doi":"10.1159/000544826","DOIUrl":"10.1159/000544826","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplant is the treatment of choice for end-stage kidney disease, with longer survival and better quality of life posttransplant. However, long-term immunosuppression comes with an increased risk of cancer and infection. Cancer is one of the leading causes of death after kidney transplant. While novel cancer therapies become available, transplant recipients are usually excluded from clinical trials.</p><p><strong>Summary: </strong>In this review, we summarize the updated knowledge on immunosuppression management in kidney transplant recipients treated with immune checkpoint inhibitors (ICIs), bispecific T-cell engager therapy, and chimeric antigen receptor (CAR)-T-cell therapies.</p><p><strong>Key messages: </strong>Transplant nephrologists should be empowered to participate in the decision-making of cancer treatment together with patients, care partners, and oncologists, by managing immunosuppression.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"154-167"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time in Target Range of Systolic Blood Pressure and Cardiovascular Disease in Patients with Chronic Kidney Disease: A Korean Nationwide Cohort Study.","authors":"Soo-Young Yoon, Su Jin Jeong, Jin Sug Kim, Hyeon Seok Hwang, Kyunghwan Jeong","doi":"10.1159/000546380","DOIUrl":"10.1159/000546380","url":null,"abstract":"<p><p><p>Introduction: Time in target range of systolic blood pressure (SBP-TTR) is the percentage of time that the SBP remains within 110-130 mm Hg. The association between the SBP-TTR and clinical outcomes in patients with chronic kidney disease (CKD) remains unclear. We evaluated the risks of cardiovascular disease (CVD), all-cause mortality, and renal events across the SBP-TTR groups.</p><p><strong>Methods: </strong>Overall, 193,289 patients with CKD who underwent at least two health checkups between 2012 and 2015 were selected from the Korean National Health Insurance Database. The patients were categorized into three categories based on their SBP-TTR levels: 76-100%, 26-75%, and 0-25%. The primary outcome was CVD risk and the secondary outcomes were all-cause mortality and progression to end-stage kidney disease (ESKD) according to SBP-TTR using Cox regression analysis.</p><p><strong>Results: </strong>Compared with patients with SBP-TTR of 76-100%, the adjusted hazard ratios (HRs) for CVD were 1.07 (95% confidence interval [CI], 1.03-1.10) and 1.09 (95% CI: 1.06-1.13) for patients with SBP-TTR of 26-75%, and 0-25%, respectively. The adjusted HR for all-cause mortality was 1.04 (95% CI: 1.003-1.07) and 1.37 (95% CI: 1.28-1.46) for patients with SBP-TTR of 26-75% and 0-25%, respectively. The adjusted HRs for ESKD progression increased gradually: 1.14-fold (95% CI: 1.07-1.21) for the SBP-TTR 26-75% group and 1.37-fold (95% CI: 1.28-1.46) for the SBP-TTR 0-25% group. For patients not taking antihypertensive medications, a lower SBP-TTR was associated with a higher risk of CVD events and ESKD progression than in those taking antihypertensive medications.</p><p><strong>Conclusion: </strong>Among patients with CKD, those with a lower SBP-TTR had a higher risk of cardiovascular events, mortality, and progression to ESKD. </p>.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"30-41"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Interleukin 22 Predicts Progression of Early Diabetic Kidney Disease.","authors":"Beatriz Fernandez-Fernandez, Takehiro Hasegawa, Yuko Saruta, Yun Li Guan, Ana Belen Sanz, Maria Dolores Sanchez-Niño, Adrian M Ramos, Jinny Sanchez-Rodriguez, Juan Francisco Navarro-Gonzalez, Alberto Ortiz","doi":"10.1159/000547738","DOIUrl":"10.1159/000547738","url":null,"abstract":"<p><strong>Introduction: </strong>The residual risk of chronic kidney disease (CKD) progression remains high in clinical trials of kidney protective drugs in patients with diabetic kidney disease (DKD).</p><p><strong>Methods: </strong>In a prospective study, we assessed whether 16 plasma and 10 urine cytokine levels can inform the residual risk of CKD progression in 93 incident patients with DKD treated by nephrology according to clinical guidelines.</p><p><strong>Results: </strong>Plasma and urine levels of 12 plasma and 7 urinary cytokines differed between patients with DKD and from healthy controls. Participants were categorized into CKD G1-G2 (preserved GFR) and CKD G3-G5 (GFR <60 mL/min/1.73 m2). After a median of 7.27 years (interquartile range, 5.34-9.56), 13/40 (32.5%) patients with CKD G1-G2 at baseline had progressed to CKD G3-G5. Progressors had higher plasma interleukin 22 (IL-22) and tumor necrosis factor-alpha (TNF-α) levels than nonprogressors. Plasma IL-22 and TNF-α levels in progressors were similar to those in patients already in CKD G3-G5 at baseline, suggesting that cytokine dysregulation precedes CKD progression. In patients with CKD G1-G2, cutoff points for plasma IL-22 and TNF-α predicted progression with an area under the curve of 0.76 and 0.77, respectively. Additionally, patients with CKD G1-G2 and plasma TNF-α or IL-22 levels equal to or above the cutoff value had significantly lower estimated glomerular filtration rate values at the end of follow-up and had more frequently progressed to a very high-risk KDIGO category. In cluster analysis, clusters displaying the highest urinary or plasma cytokine levels were associated with worse GFR outcomes.</p><p><strong>Conclusion: </strong>Plasma IL-22 and TNF-α may help identify patients with early DKD with a high residual risk of CKD progression despite treatment.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"528-540"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT-2 Inhibitors: A Deeper Dive into Their Renal Protective Properties beyond Glycemic Control and Proteinuria Reduction.","authors":"Yu An, Haitao Zhang","doi":"10.1159/000546079","DOIUrl":"10.1159/000546079","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) is highly prevalent and associated with an increasing burden on patients and the healthcare system. Its complex causes and diverse manifestations pose considerable challenges in slowing disease progression. Over the last few decades, pharmacotherapeutic strategies have primarily focused on reducing albuminuria, managing complications, and alleviating symptoms. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, known for their glycemic control and cardiovascular benefits in diabetic patients, have shown promise in renal protection, offering hope for slowing CKD progression in a broader patient population.</p><p><strong>Summary: </strong>The DAPA-CKD and EMPA-KIDNEY trials have provided compelling evidence that dapagliflozin and empagliflozin reduced the risk of a series of renal events and slowed the chronic decline of estimated glomerular filtration rate in patients with CKD, irrespective of diabetic status. The results of these trials strongly support the notion that SGLT-2 inhibitors are effective in renal protection across CKD patients with diverse primary diseases and in varying CKD risk categories. EMPA-KIDNEY also demonstrated that empagliflozin can potentially slow CKD progression in patients without albuminuria, a finding corroborated by results from several other studies. The long-term cardiorenal benefits of empagliflozin were further demonstrated in the post-trial follow-up sub-study of EMPA-KIDNEY. The synergistic effect of SGLT-2 inhibitors with other drugs that have different mechanisms of action is being researched for broader applications.</p><p><strong>Key messages: </strong>Emerging evidence underscores the potential of SGLT-2 inhibitors to benefit a wide range of CKD patients, regardless of causes and albuminuria status. Further research in this area will improve our understanding of the roles of this new class of drug in renal protection and potentially shift the paradigm of CKD management.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"53-65"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}